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Intermittent androgen suppression may be noninferior to continuous androgen deprivation

ASCO 2011 Genitourinary Cancers Symposium

ORLANDO — Intermittent androgen suppression therapy yielded similar OS outcomes as continuous androgen deprivation in a cohort of men with localized prostate cancer who had received radical radiotherapy, according to findings presented here.

Laurence Klotz, MD, chief of urology at Sunnybrook Health Sciences Center, and professor of surgery at the University of Toronto, said intermittent therapy was delivered in 8-month cycles and was restarted when PSA levels were more than 10 ng/mL during nontreatment times.

There were 690 patients in the intermittent therapy arm and 696 patients in the continuous androgen deprivation therapy arm. The median duration of follow-up was 6.9 years.

“The median OS was 8.8 years in the intermittent therapy arm and 9.1 years in the continuous therapy arm,” Klotz said. “Intermittent therapy was noninferior to continuous therapy with regard to OS. Moving forward, this should be the standard of care for these patients.”

There were 268 deaths in the intermittent therapy arm and 256 deaths in the continuous therapy arm.

There were 122 disease-related deaths in the intermittent arm vs. 97 in the androgen therapy arm. “The difference in disease-specific mortality was also nonsignificant,” Klotz said, adding that there were fewer deaths unrelated to disease in the intermittent therapy arm, 134 vs. 146.

He also reported on time to castration-resistant disease. “The curves for castration-resistant disease came together at around 10 years,” he said. “There was not much difference between the two arms.”

Apart from reduced incidence of hot flashes in the intermittent therapy group, no differences in adverse events, including myocardial events or osteoporotic fractures, were observed between the two groups.

The primary endpoint was OS. Secondary endpoints included time to hormone refractory state, quality of life, HDL and LDL cholesterol levels, duration of treatment and nontreatment intervals, time to testosterone and potency recovery, according to Klotz.

The aim of the trial was to determine whether intermittent androgen suppression could improve survival and quality-of-life outcomes in men with PSA recurrence, which was defined as more than 3 ng/ml, more than a year after radical radiotherapy.

The median number of 8-month cycles completed by the intermittent therapy patients was two (range, 1-9).

An independent review committee recommended halting the trial when prespecified noninferiority boundaries were crossed.

Initial enrollment occurred in January 1999, and the most recent follow-up was conducted in October. Patients were stratified by time since radical radiation, initial PSA, prior radical prostatectomy and prior androgen deprivation therapy.

For more information:

Disclosure: Dr. Klotz reports no relevant financial disclosures.

.PERSPECTIVE

Intermittent therapy has been a talking point for a while now. This was the largest trial by far testing this strategy. It is important because it unequivocally shows that the OS is identical between intermittent and continuous approaches. This will be the definitive trial that I cite when discussing this approach.

One possible area of concern, however, is compliance. Of course, patients are compliant during treatment times, but we also have to be careful of what is happening while they are being monitored. This requires focus on the part of the patient and the clinician.

Another caveat is that we should take note of the difference between OS and time to castration-resistant disease. The disease will be recurrent, but this study shows that it can be controlled with intermittent therapy.

A final point of note that was not reported on but that needs to be discussed is the cost-savings with intermittent treatment. It is a simple equation: Less frequent treatment and less medication translate to less money spent.

Oliver Sartor, MD
Medical Director, Tulane Cancer Center; Director, Prostate Cancer Program

Disclosure: Dr. Sartor reports no relevant financial disclosures.

PERSPECTIVE

Mark Stein, MD
Mark Stein

Intermittent androgen deprivation appears to be an acceptable alternative to continuous androgen deprivation for men with a rising PSA after definitive local therapy with radiation or a prostatectomy followed by radiation.

This study builds on several smaller studies and provides definitive evidence for the safety of intermittent androgen deprivation for men with PSA recurrence. Quality of life assessment, a secondary endpoint of the study will be reported at a future time. However, clinical experience suggests that patients off androgen deprivation have an improved sense of well being making intermittent androgen deprivation the preferred means of administering hormonal therapy in this population of men.

- Mark Stein, MD

HemOnc Today Editorial Board Member

Disclosure: Dr. Stein reports no relevant financial disclosures.

Twitter Follow HemOncToday.com on Twitter.

ASCO 2011 Genitourinary Cancers Symposium

ORLANDO — Intermittent androgen suppression therapy yielded similar OS outcomes as continuous androgen deprivation in a cohort of men with localized prostate cancer who had received radical radiotherapy, according to findings presented here.

Laurence Klotz, MD, chief of urology at Sunnybrook Health Sciences Center, and professor of surgery at the University of Toronto, said intermittent therapy was delivered in 8-month cycles and was restarted when PSA levels were more than 10 ng/mL during nontreatment times.

There were 690 patients in the intermittent therapy arm and 696 patients in the continuous androgen deprivation therapy arm. The median duration of follow-up was 6.9 years.

“The median OS was 8.8 years in the intermittent therapy arm and 9.1 years in the continuous therapy arm,” Klotz said. “Intermittent therapy was noninferior to continuous therapy with regard to OS. Moving forward, this should be the standard of care for these patients.”

There were 268 deaths in the intermittent therapy arm and 256 deaths in the continuous therapy arm.

There were 122 disease-related deaths in the intermittent arm vs. 97 in the androgen therapy arm. “The difference in disease-specific mortality was also nonsignificant,” Klotz said, adding that there were fewer deaths unrelated to disease in the intermittent therapy arm, 134 vs. 146.

He also reported on time to castration-resistant disease. “The curves for castration-resistant disease came together at around 10 years,” he said. “There was not much difference between the two arms.”

Apart from reduced incidence of hot flashes in the intermittent therapy group, no differences in adverse events, including myocardial events or osteoporotic fractures, were observed between the two groups.

The primary endpoint was OS. Secondary endpoints included time to hormone refractory state, quality of life, HDL and LDL cholesterol levels, duration of treatment and nontreatment intervals, time to testosterone and potency recovery, according to Klotz.

The aim of the trial was to determine whether intermittent androgen suppression could improve survival and quality-of-life outcomes in men with PSA recurrence, which was defined as more than 3 ng/ml, more than a year after radical radiotherapy.

The median number of 8-month cycles completed by the intermittent therapy patients was two (range, 1-9).

An independent review committee recommended halting the trial when prespecified noninferiority boundaries were crossed.

Initial enrollment occurred in January 1999, and the most recent follow-up was conducted in October. Patients were stratified by time since radical radiation, initial PSA, prior radical prostatectomy and prior androgen deprivation therapy.

For more information:

Disclosure: Dr. Klotz reports no relevant financial disclosures.

.PERSPECTIVE

Intermittent therapy has been a talking point for a while now. This was the largest trial by far testing this strategy. It is important because it unequivocally shows that the OS is identical between intermittent and continuous approaches. This will be the definitive trial that I cite when discussing this approach.

One possible area of concern, however, is compliance. Of course, patients are compliant during treatment times, but we also have to be careful of what is happening while they are being monitored. This requires focus on the part of the patient and the clinician.

Another caveat is that we should take note of the difference between OS and time to castration-resistant disease. The disease will be recurrent, but this study shows that it can be controlled with intermittent therapy.

A final point of note that was not reported on but that needs to be discussed is the cost-savings with intermittent treatment. It is a simple equation: Less frequent treatment and less medication translate to less money spent.

Oliver Sartor, MD
Medical Director, Tulane Cancer Center; Director, Prostate Cancer Program

Disclosure: Dr. Sartor reports no relevant financial disclosures.

PERSPECTIVE

Mark Stein, MD
Mark Stein

Intermittent androgen deprivation appears to be an acceptable alternative to continuous androgen deprivation for men with a rising PSA after definitive local therapy with radiation or a prostatectomy followed by radiation.

This study builds on several smaller studies and provides definitive evidence for the safety of intermittent androgen deprivation for men with PSA recurrence. Quality of life assessment, a secondary endpoint of the study will be reported at a future time. However, clinical experience suggests that patients off androgen deprivation have an improved sense of well being making intermittent androgen deprivation the preferred means of administering hormonal therapy in this population of men.

- Mark Stein, MD

HemOnc Today Editorial Board Member

Disclosure: Dr. Stein reports no relevant financial disclosures.

Twitter Follow HemOncToday.com on Twitter.

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